There have been several reports in the popular media and the medical literature emphasizing the importance of diet and exercise in preventing or controlling heart disease (Ornish. D. et al, Lancet 1990; 336:129-133), diabetes (Boule N. G. et al, JAMA 2001, 286:1218-1227), and dementia (Rovio S. et al, Lancet Neurology 2005, 4:705-711). More recently, gastric bypass surgery too has been shown to control diabetes (Adams T. D. et al, N Engl J Med 2007, 357:753-761). Less publicized is the fact that these and many other chronic diseases are accompanied by systemic inflammation, which can be measured and tracked by analyzing the blood of the affected patient for CRP (C-Reactive Protein) level. (See, e.g., Hu F. B. Et al, Diabetes 2004, 53:693-70; Libby P. Nature 2002, 420: 868-874; Ridker P. et al, N Engl J Med 2000, 342:836-843; Baumgart D. et al, Lancet 2007, 369:1627-1640; Balkwill F. et al, Lancet 2001, 357:539-545.)
A recent special issue of Technology Review (Vol. 115, No. 2, April 2012), published by the Massachusetts Institute of Technology, featured an article entitled “The Patient of the Future,” which described the efforts of Internet pioneer Larry Smarr to quantify his health parameters by tracking about 100 biomarkers. An analysis of his data over time showed that from among all biomarkers tracked, the CRP level was singularly elevated above the normal range. Smarr reportedly suffers from Crohn's disease, an inflammatory bowel disease. Over seven months, his CRP level increased from a high value of 6.1 mg/l to an even higher value of 11.8 mg/l (less than 3 mg/l is the typical accepted normal range). Within a few months of reaching this higher value, Smarr suffered severe abdominal pain, which was diagnosed as acute diverticulitis, an inflammatory disease of the colon.
The traditional treatments for the vast majority of the inflammatory diseases involve administering anti-inflammatory drugs to suppress the immune response of the patient. Nearly all of such drugs, which are mostly steroidal and generally toxic, come with unacceptable side effects. This concern limits drug usage to the minimum total doses that will suppress the symptoms at an appropriate level. Following stabilization of the symptoms, the drug doses are quickly tapered down at a prescribed schedule to minimize side effects, the consequence of which is that inflammation remains elevated and the disease is rarely cured. As an example, the prescribed anti-inflammatory treatment schedule could consist of taking successively reduced prednisone doses according to the following schedule: 40 mg/day for one week, 30 mg/day for one week, 20 mg/day for one week, 10 mg/day for one week, and 5 mg/day for one week.
In the tapering down of the doses, the hope is that suppression of the symptoms at the high doses may permit the patient's immune system to recover sufficiently at the subsequent low doses for it to overcome the disease on its own or reduce the patient's needs to lowered doses of the (toxic) drug(s) where side effects become more manageable or are measurably absent. The possibility of achieving full immunity reactivation, however, is remote in that the adrenal glands are rendered inactive as a result of administering the anti-inflammatory drugs. Any attempt to reactivate the adrenal gland requires a reduction in the ingested drug dose for an extended time, which increases the risk that the underlying disease will erupt again.
The relationship of inflammation to disease remains unknown and presents the classic chicken and egg problem—which came first? In other words, is inflammation the cause of the disease or a consequence of it. This lack of understanding has given rise to a treatment regimen that focuses on treating the symptoms instead of the underlying cause. The instant invention discloses a chemistry based model that analyzes the significance of inflammation in disease initiation and progression, and provides the basis for devising methods for treating the inflammatory disease(s).